A transposon insertion mutant of Mycobacterium fortuitum attenuated in virulence and persistence in a murine infection model that is complemented by Rv3291c of Mycobacterium tuberculosis.
Mycobacterium fortuitum is a non-tubercular fast growing pathogenic mycobacteria whose virulence factors have not been studied. Infection of M. fortuitum ATCC 6841 in a murine infection model leads to spinning of the head in 8-12 days after infection, 20-25% mortality and a constant bacillary load in the kidney of mice, suggesting persistence. From a TnphoA insertion library, a mutant MT13 was isolated which was attenuated in virulence with lesser bacterial burden, milder and delayed spinning of the head and no mortality of mice. The significant feature of the mutant was its failure to persist in kidney and thus the persistent bacillary load characteristic exhibited by the wild type strain was not observed. The insertion of transposon in MT13 was mapped in a region of the genome, which showed homology to Rv3291c of M. tuberculosis, annotated as a transcriptional regulatory factor and reported to be up regulated in nutrient starvation and anaerobic persistent states. Complementation of MT13 with rv3291c resulted in restoration of wild type characteristics including persistence in kidney suggesting the role of a Rv3291c homolog in the virulence and persistence of M. fortuitum.
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Division of Microbiology, Central Drug Research Institute, Lucknow 226001, India.
Shrivastava
Rahul
R
Srivastava
S
S
Subramanian
A R
AR
Roy
Raja
R
Srivastava
Brahm S
BS
Srivastava
Ranjana
R
D000818:Animals; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D005260:Female; D005816:Genetic Complementation Test; D006801:Humans; D007668:Kidney / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D009165:Mycobacterium Infections, Nontuberculous / Q000382:microbiology*; D019907:Mycobacterium fortuitum / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
D004251:DNA Transposable Elements; C498065:Rv3291C protein, Mycobacterium tuberculosis; D014157:Transcription Factors